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Background: Human papillomaviruses (HPV) cause several human cancers. Bivalent (Cervarix) and quadrivalent (qGardasil) HPV vaccines both contain virus-like particles of the major oncogenic HPV types 16 and 18, but also cross-protect against some nonvaccine types. However, data on long-term sustainability of the cross-reactive antibody responses to HPV vaccines are scarce.Methods: Serum samples donated 7-12 years after immunization at age 16-17 years with bivalent (n = 730) or quadrivalent (n = 337) HPV vaccine were retrieved from the population-based Finnish Maternity Cohort biobank. Serum antibody levels against HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, and 73 were determined using multiplex pseudovirion binding assay. Antibody avidity was assessed using ammonium thiocyanate treatment.Results: Seropositivity for HPV31, 33, 35, 45, 51, 52, 58, 59, 68, and 73 was increasingly common (P ≤ .001; χ 2 test for trend for each of these types) when women had high anti-HPV16 antibody levels. For 8 nonvaccine HPV types seropositivity was more common among recipients of bivalent than quadrivalent vaccine, in particular for HPV31, 35, 45, 51, 52, and 58 (P < .001). Antibody avidity was higher in the quadrivalent vaccine recipients for HPV6, 11, and two of the nonvaccine types, but lower for HPV16 and 18 (P < .001).Conclusions: Both vaccines elicit cross-reactive antibodies detectable even 12 years after vaccination. Cross-reactive seropositivity is more common in women with high anti-HPV16 antibody response and in the bivalent vaccine recipients. [ABSTRACT FROM AUTHOR]

Clinical trial data and real-world evidence suggest that the AS04-adjuvanted vaccine targeting human papillomavirus types 16 and 18 (AS04-HPV-16/18) vaccine provides nearly 90% protection against cervical intraepithelial neoplasia grade 3 or higher irrespective of type, among women vaccinated before sexual debut. This high efficacy is not fully explained by cross-protection. Although AS04-HPV-16/18 vaccination does not affect clearance of prevalent infections, it may accelerate clearance of newly acquired infections. We pooled data from 2 large-scale randomized controlled trials to evaluate efficacy of the AS04-HPV-16/18 vaccine against clearance of nontargeted incident infections. Results of our analysis do not suggest an effect in expediting clearance of incident infections. [ABSTRACT FROM AUTHOR]

The elimination of cervical cancer rests on high efficacy of human papillomavirus (HPV) vaccines. The HPV type distribution among cases of invasive cervical cancer (ICC) is used to make predictions about the impact of eliminating different types of HPV, but accumulating evidence of differences in age-specific cancer incidence by HPV type exists. We used one of the largest population-based series of HPV genotyping of ICCs (n  = 2,850; Sweden, 2002–2011) to estimate age-specific ICC incidence by HPV type and obtain estimates of the cancer-protective impact of the removal of different HPV types. In the base case, the age-specific ICC incidence had 2 peaks, and the standardized lifetime risk (SLTR, the lifetime number of cases per birth cohort of 100,000 females) for HPV-positive ICC was 651 per 100,000 female births. In the absence of vaccine types HPV 16 and HPV 18, the SLTR for ICC was reduced to 157 per 100,000 female births (24% of HPV-positive SLTR). Elimination of all 9 types that can currently be vaccinated against reduced the remaining SLTR to 47 per 100,000 female births (7%), the remaining ICC incidence only slowly increasing with age. In conclusion, after elimination of vaccine-protected HPV types, very few cases of ICC will be left, especially among fertile, reproductive-age women. [ABSTRACT FROM AUTHOR]

Less frequent cervical cancer screening in human papillomavirus (HPV) vaccinated birth cohorts could produce considerable savings without increasing cervical cancer incidence and loss of life‐years. We report here the baseline findings and interim results of safety and accuracy of infrequent screening among HPV16/18 vaccinated females. The entire 1992–1994 birth‐cohorts (30,139 females) were invited to a community‐randomized HPV16/18‐vaccination trial. A total of 9,482 female trial participants received HPV16/18‐vaccination in 2007–2009 at age of 13–15. At age 22, 4,273 (45%) of these females consented to attend a randomized trial on frequent (ages 22/25/28; Arm 1: 2,073 females) vs. infrequent screening (age 28; Arm 2: 2,200 females) in 2014–2017. Females (1,329), who had got HPV16/18 vaccination at age 18 comprised the safety Arm 3. Baseline prevalence and incidence of HPV16/18 and other high‐risk HPV types were: 0.5% (53/1,000 follow‐up years, 104) and 25% (2,530/104) in the frequently screened Arm 1; 0.2% (23/104) and 24% (2,413/104) in the infrequently screened Arm 2; and 3.1% (304/104) and 23% (2,284/104) in the safety Arm 3. Corresponding prevalence of HSIL/ASC‐H and of any abnormal cytological findings were: 0.3 and 4.2% (Arm 1), 0.4 and 5.3% (Arm 2) and 0.3 and 4.7% (Arm 3). Equally rare HSIL/CIN3 findings in the infrequently screened safety Arm A3 (0.4%) and in the frequently screened Arm 1 (0.4%) indicate no safety concerns on infrequent screening despite the up to 10 times higher HPV16/18 baseline prevalence and incidence in the former. What's new? As the first generation of girls vaccinated against HPV reach adulthood, it's time to re‐evaluate screening recommendations. Reducing the frequency of screenings could save money without increasing cervical cancer incidence. Here, the authors collected baseline data on the safety of less frequent cervical cancer screenings. They conducted a randomized trial of Finnish women born in 1992‐1994 and vaccinated against HPV16/18, in which participants are screened either once or three times by age 28. At baseline and the first safety interim analyses they found no difference in the incidence of HSIL/CIN3 lesions between the two groups, suggesting that infrequent screening for HPV‐vaccinated women does not compromise safety. [ABSTRACT FROM AUTHOR]

We studied effectiveness of the AS04‐adjuvanted HPV‐16/18 (AS04‐HPV‐16/18) vaccine against human papillomavirus (HPV) oropharyngeal infections associated with the increase of head/neck cancers in western countries. All 38,631 resident adolescents from 1994 to 1995 birth cohorts of 33 Finnish communities were invited in this community‐randomized trial (NCT00534638). During 2008–2009, 11,275 girls and 6,129 boys were enrolled in three arms of 11 communities each. In Arm A, 90% of vaccinated girls/boys, and in Arm B, 90% of vaccinated girls received AS04‐HPV‐16/18 vaccine. Other Arm A/B and all Arm C vaccinated participants received control vaccine. All Arm A participants and Arm B female participants were blinded to vaccine allocation. Oropharyngeal samples were analyzed from 4,871 18.5‐year‐old females who attended follow‐up visit 3–6 years postvaccination. HPV DNA prevalence was determined by SPF‐10 LiPA and Multiplex type‐specific PCR. Total vaccine effectiveness (VE) was defined as relative reduction of oropharyngeal HPV prevalence in pooled Arms A/B HPV‐vaccinated females vs. all Arm C females. VE against oropharyngeal HPV‐16/18, HPV‐31/45 and HPV‐31/33/45 infections were 82.4% (95% confidence intervals [CI]: 47.3–94.1), 75.3% (95%CI: 12.7–93.0) and 69.9% (95% CI: 29.6–87.1), respectively. In conclusion, the AS04‐HPV‐16/18 vaccine showed effectiveness against vaccine and nonvaccine HPV‐types oropharyngeal infections in adolescent females up to 6 years postvaccination. What's new? The incidence of oropharyngeal cancers due to human papillomavirus (HPV) infection is increasing in Western countries. However, the efficacy of HPV vaccines against oropharyngeal infection is not well documented. Based on a large community‐randomized trial in Finland, the authors report high effectiveness (82.4%) of Cervarix vaccine against oropharyngeal HPV‐16/18 infection and moderate effectiveness against non‐vaccine types HPV‐31/33/45 infection in female adolescents. The protective effects were observed up to 6 years after vaccination. These results provide further evidence that HPV vaccination holds the potential to reduce oral HPV infection, thereby offering protection against HPV‐related head and neck cancers. [ABSTRACT FROM AUTHOR]

Oncogenic non‐vaccine human papillomavirus (HPV) types may conceivably fill the vacated ecological niche of the vaccine types. The likelihood of this may differ by the risk of acquiring HPV infections. We examined occurrence of HPV types among vaccinated and unvaccinated subgroups of 1992–1994 birth cohorts with differing acquisition risks up to 9 years post‐implementation of HPV vaccination in 33 Finnish communities randomized to: Arm A (gender‐neutral HPV16/18 vaccination), Arm B (girls‐only HPV16/18 vaccination and hepatitis B‐virus (HBV) vaccination of boys), and Arm C (gender‐neutral HBV vaccination). Out of 1992–1994 born resident boys (31,117) and girls (30,139), 8,618 boys and 15,615 girls were vaccinated, respectively, with 20–30% and 50% coverage in 2007–2009. In 2010–2013, 8,868 HPV16/18 and non‐HPV vaccinated females, and in 2014–2016, 5,574 originally or later (2010–2013) HPV16/18 vaccinated females attended two cervical sampling visits, aged 18.5 and 22‐years. The samples were typed for HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68 using PCR followed by MALDI‐TOF MS. HPV prevalence ratios (PR) between Arms A/B vs. C were calculated for Chlamydia trachomatis positives (core‐group), and negatives (general population minus core group). At both visits the vaccine‐protected HPV type PRs did not significantly differ between the core‐group and non‐core group. Among the vaccinated 18‐year‐olds, HPV51 occurrence was overall somewhat increased (PRcore = 1.4, PRnon‐core. = 1.4) whereas the HPV52 occurrence was increased in the core‐group only (PRcore = 2.5, PRnon‐core = 0.8). Among the non‐HPV vaccinated 18‐year‐olds, the HPV51/52 PRs were higher in the core‐group (PRcore = 3.8/1.8, PRnon‐core = 1.2/1.1). The 22‐year‐olds yielded no corresponding observations. Monitoring of the sexual risk‐taking core‐group may detect early tendencies for HPV type replacement. What's new? Oncogenic non‐vaccine human papillomavirus (HPV) types may conceivably fill the vacated ecological niche of the vaccine types‐‐a phenomenon which could undermine national HPV vaccination programs and warrants surveillance. The high sexual activity core‐group, which is permissive for faster transmission dynamics, may be more susceptible to HPV type replacement. Here, the authors report that in the core‐group defined by Chlamydia trachomatis positivity, among non‐HPV vaccinated women high‐risk HPV51 and HPV52 were increased four years post‐vaccination. In the core‐group of HPV16/18 vaccinated women HPV52 only was increased. Monitoring of the sexual risk‐taking core‐group may detect early tendencies for HPV type replacement. [ABSTRACT FROM AUTHOR]

Background: Most cervical cancers are caused by vaccine-preventable infections with human papillomaviruses (HPV). The HPV prophylactic vaccines Gardasil and Cervarix have been widely used for >10 years and are reported to induce high antibody levels. A head-to-head comparison of the antibody responses induced by the 2 vaccines has been performed only up to 5 years.Methods: Among 3300 Finnish females aged 16-17 years who got 1 of the 2 HPV vaccines in phase 3 licensure trials, virtually all consented to registry-based long-term follow-up. Linkage with the Finnish Maternity Cohort found that they donated >2500 serum samples up to 12 years later. Sera of 337 (38.6%) Gardasil and 730 (30.3%) Cervarix vaccine recipients were retrieved from the Finnish Maternity Cohort biobank and type-specific anti-HPV antibody levels were determined using in-house multiplexed heparin-HPV pseudovirion Luminex assay.Results: Anti-HPV-16 and anti-HPV-18 antibody levels remained stable and above natural infection-related antibody levels for up to 12 years for most vaccine recipients. The median antibody levels were higher among Cervarix recipients 7-12 years post vaccination (P < .0001).Conclusions: The stability of vaccine-induced antibody levels is in accordance with the high long-term protection reported previously. The differences in antibody levels induced by the 2 vaccines imply that continued follow-up to identify possible breakthrough cases and estimation of the minimal protective levels of serum antibodies is a research priority. [ABSTRACT FROM AUTHOR]

Introduction: Infections with oncogenic human papillomaviruses (HPV) globally cause about 9% of cancers in females and 1% of cancers in males. HPV disease burden can be effectively controlled by prophylactic HPV-vaccination provided it has high impact. Areas covered: A unique series of biobank-based and health registry-based studies that exploit randomized intervention cohorts has provided data on population-level safety of HPV vaccination, duration of vaccine-induced protection and impact of gender-neutral HPV vaccination, providing a scientific basis for policies to eradicate oncogenic HPV types and associated diseases worldwide. Expert commentary: The ultimate goal of HPV vaccination is the eradication of high-risk (hr) HPVs. Seventy-five percent coverage gender-neutral vaccination of early adolescents will rapidly eradicate also HPV16 from the general population. [ABSTRACT FROM AUTHOR]